A primer on the hormone-free interval for combined oral contraceptives

Abstract

Background:

The dosing, schedules, and other aspects of combined oral contraceptive (COC) design have evolved in recent years to address a variety of issues including short- and long-term safety, bleeding profiles, and contraceptive efficacy. In particular, several newer formulations have altered the length of the hormone-free interval (HFI), in order to minimize two key undesired effects that occur during this time: hormone-withdrawal-associated symptoms (HWaS) and follicular development.

Objective:

This primer reviews our current understanding of the key biological processes that occur during the HFI and how this understanding has led to changes in the dosing and schedule of newer COC formulations.

Main message:

In brief, HWaS are common, underappreciated, and a likely contributor to COC discontinuation; because of this, shortening the HFI and/or supplementing with estrogen during the progestin-free interval may provide relief from these symptoms and improve adherence. A short HFI (with or without estrogen supplementation) may also help maintain effective follicular suppression and contraceptive efficacy, even when the overall dose of estrogen throughout the cycle is low.

Conclusions:

Taken together, the available data about HWaS and follicular activity during the HFI support the rationale for recent COC designs that use a low estrogen dose and a short HFI. The availability of a variety of COC regimens gives physicians a range of choices when selecting the most appropriate COC for each woman’s particular priorities and needs.

Keywords: :

• Estrogens
• Oral contraceptives, combined
• Ovarian follicles
• Progestins

Transparency

Declaration of funding

The creation of this article was funded by Actavis Specialty Pharmaceuticals Co. who played no part in the research and writing of the manuscript.

Declaration of financial/other relationships

V.B. has disclosed that she has received honoraria and/or consulted for Bayer, Merck, Pfizer, Novartis, Novo Nordisk, Amgen, and Actavis, and is on the Board of Immunize Canada and the Women’s Brain Health Initiative. B.A.H. has disclosed that he has participated in advisory boards for Actavis and Bayer, and acted as a speaker for Actavis, Bayer, and Merck.

CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

The authors would like to acknowledge the conceptual and editorial support provided by John Ashkenas PhD and Sarah von Riedemann MSc of SCRIPT, Toronto, Ontario, Canada.